Almost two years since the pandemic began, and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) remains a part of everyday life for most individuals worldwide. While vaccines are becoming more available, and infection rates continue to decline, we still do not have a viable treatment option for those who become infected. We have targeted the main protease of SARS-CoV-2 due to its crucial role in the replication cycle of the virus. After infection of the virus into a cell, the viral RNA can be immediately translated into viral protein by the host cell machinery without need for further modification. The viral RNA produces its proteins in multiple reading frames as large polyproteins that must be cleaved into the respective proteins to become active. The main protease (Mpro) performs this function, cleaving between glutamine and serine in the sequence VLQSG to produce the active viral proteins. The requirement of these polyproteins to be cleaved places Mpro in an ideal position as a drug target. We have used a molecular docking approach to identify compounds, some commercially available, that show potential binding to Mpro. The function of the main protease is assayed with a commercially available peptide containing the cleavage sequence of the Mpro, in the absence and presence of the possible inhibitors that are commercially available. This study will help identify molecules that bind to and inhibit the function of Mpro, which will allow us to test and optimize structures to develop effective drugs against SARS-CoV-2.

Identifying and testing commercially available ligands against SARS-CoV-2 Mpro

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.